We are learning a whole lot about our capsids and our payloads. We’ll certainly employ all of that. A lot of it will be transferable, but some will be disease and target specific.
Dr. Al Sandrock: And I would only add — thanks, Todd. Now I understand the question, I think. Yes, I would add that for tau, we don’t really care too much about knocking down in astrocytes. It’s mainly the neuron that we want to knock down the expression of tau. But Todd’s right, they’re both vectorized siRNA. So we’ll learn a lot from the first program that we hope will apply to the second. I would also say that the capsids, we could use the same capsid. We can use different capsids against different receptors or we can use different capsids again for the same receptor, which we already know that Receptor X is a human homologue. So yes, I think there’s a high potential for lots of learnings from our first program that may help us with the second and third and so forth programs.
Yanan Zhu: Great. That’s super helpful. And lastly, I was wondering if I can ask a quick question, the Receptor X efforts. I’m mainly interested in at what stage do you think this will be an asset that is ready to pursue a partnership interest. Is there a particular milestone in terms of preclinical evidence, or could the interest come in at any time and you’re ready to discuss it at any time?
Dr. Al Sandrock: Well, look, I’m always ready to discuss potential partnerships with good partners, always ready, door’s always open. For me, what I want to see is in vivo evidence that we can shuttle a macro molecule, such as a nucleic acid or a protein across the BBB and get the desired effect, pharmacodynamic effect in the brain. If we see that, now I’m pretty — I’m even more excited. And then we can start to think about, okay, what do we want to shuttle across and which targets do we want to pursue? But it’s that proof of concept, if you will, if you can use the leverage Receptor X to shuttle things across the BBB and produce a biological effect in the brain that will trigger a whole bunch of things, I believe, including potential partnership discussions, as you mentioned.
Operator: [Operator Instructions] And our next question coming from the line of Sumant Kulkarni with Canaccord.
Sumant Kulkarni: Thanks for taking my questions. Both are on the TAU01 antibody. You alluded to this a little bit, but was more related to the potential outcomes of a trial. But at this stage, how are you conceptualizing any tau-based or to tau burden-based cutoff to recruit patients into your clinical trials?
Dr. Al Sandrock: Yes. I was thinking that we would probably want people who have — people will be the equivalent of Braak stage 2 maybe also Braak stage 3, but right now, I’m honing in on Braak stage 2, which can be defined by tau PET imaging to enroll those patients and then see whether or not we can block the progression to stage 3 and 4, if you will. That’s how we’re thinking about it now. Still — we’re still doing a lot of the thinking around it as well as consulting with experts and investigators but that’s conceptually how we’re thinking about it now. Is that what you were asking? Does that answer your question, Sumant.
Sumant Kulkarni: Yes, somewhat. But a little bit of a follow-up to that is, do you think blood-based biomarkers will evolve enough to be helpful to you in your trial inclusion program?
Dr. Al Sandrock: I think that blood-based biomarkers, we can get clarity as to which blood-based biomarker links up to Braak stage 2 that would be helpful. It may be — what I can imagine us doing is starting with a — starting the screening for patients with a blood test using a blood-based biomarker and then taking those patients that are — that qualify based on that and then doing tau PET imaging to be sure that they have the right stage. So, I could see it as a sequential sort of straining process, if you will, starting with more feasible and easier and cheaper blood tests and then moving to the more complex and more expensive tau PET imaging to select the right patients.
Sumant Kulkarni: Got it. And then given what you know so far about your antibody, are there any special considerations we should be aware of on your GLP tox studies, or are these relatively conventional ones?
Dr. Al Sandrock: Well, let me start by saying that we did have an interaction with FDA earlier this year. Second, I would say that there’s one, word conventional is a little tough, because one of the things that we like of our antibody is that it’s very specific for pathological forms of tau. In other words, it does not bind normal tau that we all have in our bodies and that every animal has. So, if you want to look at on-target toxicity, it’s kind of hard to do that in a wild-type animal, which is what’s typically used for tox studies. So, you can imagine that’s a little bit more complicated than, I would say, the conventional toxicology studies. But we’ve taken all that into account, and we’ve had our interaction with FDA. And we think we’re on track for an IND as we indicated in the first half of next year.
Operator: Our next question coming from the line of Divya Rao with TD Cowen.
Divya Rao: Most of mine have been answered, but — you guys have talked a lot about potential partnerships and how those discussions are constantly ongoing. But, going forward, is the focus going to be more on maybe generating a proof of concept in an early stage trial before initiating discussions with partners to pursue those larger later-stage trials, or can we still think of it as like out-licensing programs that are identified through the TRACER platform? And then, I have a follow-up.
Dr. Al Sandrock: Yes. So I would say that right now, we — as you’ve seen, we’ve done a variety of partnerships, including sort of relatively simple capsid licensing arrangements as well as partnerships around named programs, such as GBA1 program, for example. And we’re open to either type of partnership. And your question was, I think, are we going to increasingly look to get to proof of concept before we partner. Well, as we get more and more the financial wherewithal to do that, we may want to get to proof of concept. But I never rule out anything. We’re open to talking to any partner about any type of deal that makes sense for us, for our shareholders and for the patients most importantly. We’re conscious of the fact that, of course, the further you go in development, the more value is created.
But on the other hand, there is more risk that you absorb as we get to that proof of concept. So, it’s always — we’re always thinking about all these things, value, risk, et cetera.
Divya Rao: That’s helpful. And then, on the tau program, with the top studies done, are there — I guess what else needs to be done before the IND is ready to be submitted? Is it mostly just compiling everything and putting it all together?
